AR084319A1 - MicroRNA INHIBITORS (miRNA OR miR) THAT INCLUDE BLOCKED NUCLEOTIDES - Google Patents

MicroRNA INHIBITORS (miRNA OR miR) THAT INCLUDE BLOCKED NUCLEOTIDES

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Publication number
AR084319A1
AR084319A1 ARP110104716A ARP110104716A AR084319A1 AR 084319 A1 AR084319 A1 AR 084319A1 AR P110104716 A ARP110104716 A AR P110104716A AR P110104716 A ARP110104716 A AR P110104716A AR 084319 A1 AR084319 A1 AR 084319A1
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AR
Argentina
Prior art keywords
mir
mirna
oligonucleotides
oligonucleotide
nucleotides
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Application number
ARP110104716A
Other languages
Spanish (es)
Inventor
Christina Dalby
William S Marshall
Rooij Eva Van
Rusty Montgomery
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Miragen Therapeutics
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Publication date
Application filed by Miragen Therapeutics filed Critical Miragen Therapeutics
Publication of AR084319A1 publication Critical patent/AR084319A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/11—Antisense
    • C12N2310/113—Antisense targeting other non-coding nucleic acids, e.g. antagomirs
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/315—Phosphorothioates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/323—Chemical structure of the sugar modified ring structure
    • C12N2310/3231—Chemical structure of the sugar modified ring structure having an additional ring, e.g. LNA, ENA
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2525/00—Reactions involving modified oligonucleotides, nucleic acids, or nucleotides
    • C12Q2525/10—Modifications characterised by
    • C12Q2525/204—Modifications characterised by specific length of the oligonucleotides
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/178—Oligonucleotides characterized by their use miRNA, siRNA or ncRNA

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Biochemistry (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Cardiology (AREA)
  • Biophysics (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Epidemiology (AREA)
  • Hospice & Palliative Care (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)

Abstract

Oligonucleótidos modificados por medios químicos que pueden inhibir la expresión (por ejemplo, la abundancia) del miARN de la familia miR-208, lo que abarca miR-208a, miR-208b y/o miR-499. Oligonucleótidos que pueden inhibir específicamente la expresión o la abundancia de miR-208a, miR208b y/o miR-499. Composiciones farmacéuticas que comprenden estos oligonucleótidos. Métodos para tratar pacientes que padecen afecciones o trastornos donde participa el miARN de la familia miR-208, tales como las afecciones cardiovasculares. Los oligonucleótidos presentan ventajas relacionadas con la potencia, la eficiencia de la administración, la especificidad por el blanco, la toxicidad y/o la estabilidad.Reivindicación 1: Un oligonucleótido caracterizado porque comprende una secuencia de nucleótidos que es sustancialmente complementaria a una secuencia de nucleótidos de miR-208a o miR-208b humano, y que tiene una mezcla de nucleótidos bloqueados y no bloqueados, en donde la longitud del oligonucleótido y el número y la posición de nucleótidos bloqueados es tal que el oligonucleótido reduce la actividad de miR-208a, miR-208b, y/o miR-499 a una concentración de oligonucleótido de aproximadamente 50 nM o menos en un ensayo de luciferasa in vitro, o a una dosis de 25 mg/kg o menos en un modelo de ratón.Chemical modified oligonucleotides that can inhibit the expression (eg, abundance) of the miRNA of the miR-208 family, which encompasses miR-208a, miR-208b and / or miR-499. Oligonucleotides that can specifically inhibit the expression or abundance of miR-208a, miR208b and / or miR-499. Pharmaceutical compositions comprising these oligonucleotides. Methods to treat patients suffering from conditions or disorders where the miRNA of the miR-208 family participates, such as cardiovascular conditions. Oligonucleotides have advantages related to potency, administration efficiency, target specificity, toxicity and / or stability. Claim 1: An oligonucleotide characterized in that it comprises a nucleotide sequence that is substantially complementary to a nucleotide sequence of human miR-208a or miR-208b, and having a mixture of blocked and unblocked nucleotides, wherein the length of the oligonucleotide and the number and position of blocked nucleotides is such that the oligonucleotide reduces the activity of miR-208a, miR-208b, and / or miR-499 at an oligonucleotide concentration of approximately 50 nM or less in an in vitro luciferase assay, or at a dose of 25 mg / kg or less in a mouse model.

ARP110104716A 2010-12-15 2011-12-15 MicroRNA INHIBITORS (miRNA OR miR) THAT INCLUDE BLOCKED NUCLEOTIDES AR084319A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US42345610P 2010-12-15 2010-12-15
US201161495224P 2011-06-09 2011-06-09

Publications (1)

Publication Number Publication Date
AR084319A1 true AR084319A1 (en) 2013-05-08

Family

ID=45771875

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP110104716A AR084319A1 (en) 2010-12-15 2011-12-15 MicroRNA INHIBITORS (miRNA OR miR) THAT INCLUDE BLOCKED NUCLEOTIDES

Country Status (14)

Country Link
US (2) US8642751B2 (en)
EP (1) EP2652151A2 (en)
JP (1) JP2014504857A (en)
KR (1) KR20140004646A (en)
CN (1) CN103380215A (en)
AR (1) AR084319A1 (en)
AU (1) AU2011343720A1 (en)
BR (1) BR112013012319A2 (en)
CA (1) CA2817371A1 (en)
EA (1) EA201370139A1 (en)
MX (1) MX2013005875A (en)
SG (1) SG190355A1 (en)
WO (1) WO2012083005A2 (en)
ZA (1) ZA201303422B (en)

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